Success Then Rapidly Moving Relapse in Spite of MB-12

First post to this forum/blog; been lurking for about six months. Learned a lot about treating myself with measurable success but I’ve recently had a setback after titrating sublingual Methyl B-12 and Adeno B-12 concurrently while taking a low dose of L5MTHF. (Nonetheless, I’ve been able to help my daughter who has been mostly bedridden for 8 years with ME/CFS). Thanks to all contributors!

Briefly my story:
Diagnosed 8 years ago w/B-12 insufficiency treated with 1,000 mcg of Cyano B-12. Starting in the ‘70’s, decades of absent ankle/knee jerks. Gradually developed numbness in feet and legs. EMG/NCVs showed substantial signal latency and conduction block. Had chronic connective tissue problems (tendon tears, pain), sinus infections. Got diagnosis of Distal Axonopathy (sensorimotor, stocking-glove distribution, symmetric, progressive, not immune-mediated). I do not know if I have ME/CFS. I do know some of this site’s protocols have helped me.

Over the years, Vet Affairs and three outside neurologists agreed on DA diagnosis, but not the etiology:
Vet Affairs: toxin exposure (Agent Orange)
Other Neuro #1: don't know but probably diabetes (I.e., subclinical)
Other Neuro #2: looks a lot like diabetes
Other Neuro #3: don’t know but you do NOT have diabetes

I got really tired of going to Neuros, just to have them measure my deterioration so I began to do some research. I found this site and, making a long story short, I stopped taking Cyano B-12 and started taking (5,000 mcg Kirkland) MB-12. The NEXT MORNING my calves weren’t painful, walking was more “solid”, and things continued to improve.

Several times over the past months I have tried to add AB-12 but felt bad and had to stop. Was able to titrate MB-12 to 15,000 mcg. Things were going well. Progressive nature of numbness in feet, legs and hands stopped; motor deficits substantially improved.

Three weeks ago I began adding AB-12 and upping MB-12. I reached 50,000 mcg MB-12 and 15,000 mcg AB-12, and continuing with my standard 200mcg L5MTHF. I increased MB-12 in hopes of getting a greater effect in my mostly numb feet. However, I noticed the numbness in my feet was slowly increasing and is now advancing so quickly that I can tell the difference each morning as I wake up. Also, aches and pains that were common before I started methylation that taking MB-12 eliminated, have returned.

When the result of my supplements regimen goes south, I return to baseline, so a week ago I went back to 5,000 mcg of MB-12, no AB-12, no L5MTHF. Titrated MB-12 to 20,000 mcg, eventually L5MTHF to 200 mcg.

I read more on Paradoxical Folate Deficiency and 2 days ago went to 400 mcg with L5MTHF, then 800 mcg today. I feel better but the numbness still appears to be progressing, now with renewed Pudendal nerve involvement.

Question: Does this scenario look like paradoxical folate deficiency? Freddd, is this somewhat similar to the neurological problems you are dealing with?

It sounds as though you are pretty far out of balance regarding MB12/Methylfolate and there are numerous cofactors that need attention as well especially K and Zn and B6. You need to reread the methylation protocol, folate deficiency is not good as it would cause a rise in serum homocysteine and could lead to arterial problems.

You have reached a tipping point where you have run another cofactor down and effectively blocked the system at a different point.

It sounds as though you are pretty far out of balance regarding MB12/Methylfolate and there are numerous cofactors that need attention as well especially K and Zn and B6. You need to reread the methylation protocol, folate deficiency is not good as it would cause a rise in serum homocysteine and could lead to arterial problems.

You have reached a tipping point where you have run another cofactor down and effectively blocked the system at a different point.

First post to this forum/blog; been lurking for about six months. Learned a lot about treating myself with measurable success but I’ve recently had a setback after titrating sublingual Methyl B-12 and Adeno B-12 concurrently while taking a low dose of L5MTHF. (Nonetheless, I’ve been able to help my daughter who has been mostly bedridden for 8 years with ME/CFS). Thanks to all contributors!

Briefly my story:
Diagnosed 8 years ago w/B-12 insufficiency treated with 1,000 mcg of Cyano B-12. Starting in the ‘70’s, decades of absent ankle/knee jerks. Gradually developed numbness in feet and legs. EMG/NCVs showed substantial signal latency and conduction block. Had chronic connective tissue problems (tendon tears, pain), sinus infections. Got diagnosis of Distal Axonopathy (sensorimotor, stocking-glove distribution, symmetric, progressive, not immune-mediated). I do not know if I have ME/CFS. I do know some of this site’s protocols have helped me.

Over the years, Vet Affairs and three outside neurologists agreed on DA diagnosis, but not the etiology:
Vet Affairs: toxin exposure (Agent Orange)
Other Neuro #1: don't know but probably diabetes (I.e., subclinical)
Other Neuro #2: looks a lot like diabetes
Other Neuro #3: don’t know but you do NOT have diabetes

I got really tired of going to Neuros, just to have them measure my deterioration so I began to do some research. I found this site and, making a long story short, I stopped taking Cyano B-12 and started taking (5,000 mcg Kirkland) MB-12. The NEXT MORNING my calves weren’t painful, walking was more “solid”, and things continued to improve.

Several times over the past months I have tried to add AB-12 but felt bad and had to stop. Was able to titrate MB-12 to 15,000 mcg. Things were going well. Progressive nature of numbness in feet, legs and hands stopped; motor deficits substantially improved.

Three weeks ago I began adding AB-12 and upping MB-12. I reached 50,000 mcg MB-12 and 15,000 mcg AB-12, and continuing with my standard 200mcg L5MTHF. I increased MB-12 in hopes of getting a greater effect in my mostly numb feet. However, I noticed the numbness in my feet was slowly increasing and is now advancing so quickly that I can tell the difference each morning as I wake up. Also, aches and pains that were common before I started methylation that taking MB-12 eliminated, have returned.

When the result of my supplements regimen goes south, I return to baseline, so a week ago I went back to 5,000 mcg of MB-12, no AB-12, no L5MTHF. Titrated MB-12 to 20,000 mcg, eventually L5MTHF to 200 mcg.

I read more on Paradoxical Folate Deficiency and 2 days ago went to 400 mcg with L5MTHF, then 800 mcg today. I feel better but the numbness still appears to be progressing, now with renewed Pudendal nerve involvement.

Question: Does this scenario look like paradoxical folate deficiency? Freddd, is this somewhat similar to the neurological problems you are dealing with?

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Hi ChetRoi,

Yes, these are very similar neurological problems. I use numbness etc as my measure of which way things are going. Take a look at that new post I did on proportionality between MeCbl and AdoCbl etc. and the effects of ratio on relative effectiveness. I find it takes me about 15mg of Metafolin daily to get me completely out of folate insufficiency art all levels. Currently I need about 1800mg a day to stay out of trouble on potassium. These can go WAY up a few days after healing starts. It is not anything like a linear proportion. It's a sudden jump. The Kirkland MeCbl I did not find to be qualitatively suitable for substantial CNS healing. You can increase Metafolin by 4800mcg a day to easily see the effects. It aids retention of B12 and maybe is involved in transport into the CNS. It is going to be essential to heal the nerves, along with LCF and omega3 oils and other things.

Go back to where it was last effective. Get things going, then improve incrementally. Get yourself 10 different brands and take a different one for 3 days ladder tournament style. If Number 3 is better than 2 or 1, then try 4. Then go back to 3 and determine which is better. Always go back to a stable healing condition before trying the next brand. Find the best 2 or maybe three and order a different 10 brands and repeat against the 2-3 remaining until you find a brand that knocks your socks off the best of any of them. Get back to healing, balance out methylfolate and potassium. Either or both of these going low are flags indicating healing is happening. You want to heal that Pudendal nerve. Numbness of this kind is often demyelination. Healing this is tricky and there are no guarantees. First get that healing in general going. Then we work for incremental improvements from there. At the worst I couldn't feel position of my feet and I was falling. It took me 10mg 3x per day of injections of MeCbl, protected from light etc. to recover control of my toes, feeling foot location, feeling in the skin, some feeling of muscles and no more falling and Pudendal nerve healing.

The potassium and/or folate insufficiency symptoms are below. They should be able to help you decide what might be happening.

Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (Cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (Hydroxycobalamin).

There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.

It could be healing crisis, low potassium, or the dreaded paradoxical folate deficiency. Keep in mind that methylation is an up and down process of healing. It is not a straight shot trajectory to perfect health. Some of the times symptoms may actually worsen as a sign of healing, it is actually the norm with many chronic conditions after all. It takes quite a bit of work to get the whole system rolling again after all.

You were taking a HUGE amount of ab12, and Methyl b12 compared to the methyl folate. It may help to really bump the methyl folate up and see how you feel, also important to really bump up the potassium and other co factors. The RDV of Potassium is 4000mg a day. 198g is like 1/4 a banana. Try and get a potassium supplement powder and hit at least 1500mg of supplemental potassium a day. Of course given you don't have any kidney problems or other medical conditions contridicting its use. Talk to a doctor before starting anything new. I am not a medical doctor nor condoning medical advice.

Starting in the ‘70’s, decades of absent ankle/knee jerks. Gradually developed numbness in feet and legs. EMG/NCVs showed substantial signal latency and conduction block. Had chronic connective tissue problems (tendon tears, pain), sinus infections. Got diagnosis of Distal Axonopathy (sensorimotor, stocking-glove distribution, symmetric, progressive, not immune-mediated). I do not know if I have ME/CFS. I do know some of this site’s protocols have helped me.

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Hi @ChetRoi
In light of your history and symptoms I would consider seeing an experienced LLMD and have thorough testing for Lyme and all possible co-infections. It could explain a lot of your neurological symptoms. Best wishes.

If you are taking high doses of b12 you also have to take a b-complex. Deficiencies of all b vitamins can give neurological problems, not only b12. Also take methylfolate, zinc,magnesium and potassium.
For me these are the most important.

As Freddd indicated, the first order of business for me is to get back to the regimen that was effective. This required a careful reading of my daily (excel) log since intermittent remarks started about three months ago showing I was questioning whether foot numbness was worsening.

The log shows a point three months ago when I was taking 5 mg of Kirkland MB-12. At that time, I was one week off of the second trial (which lasted two weeks) of 3mg of AB-12. I was also one week into a 99mg dose of potassium, the first potassium I had taken. (I routinely eat two bananas each day, all totaling about 1,000 mg of K at that time.)

I’m hopeful that my system will respond as it did then, although my chemistry is clearly not what it was at that time. I intend to stick to this (earlier) regimen plus 400 mg of methylfolate and a complex multivitamin for perhaps up to a month, depending upon how quickly my feet and legs continue to worsen in numbness. However, if this level of methylation doesn’t hold the line on even collateral symptoms, I will step up the MB-12 in concert with corresponding amounts of potassium and methylfolate, per recommendations.

I think this is my best play. I am interested in hearing opinions on this plan, contrary or not.

@ChetRoi Keeping my eye on your progress as the numbness in foot is something that devils me. Actually goes down my right leg on the outside, spreads across my baby toe and I think the one next too, and then fans out across the bottom of my foot…..it always feels like I am walking on gravel…….always brushing off non existing stuff that feels like is on the bottom of my foot but nothing is there

As Freddd indicated, the first order of business for me is to get back to the regimen that was effective. This required a careful reading of my daily (excel) log since intermittent remarks started about three months ago showing I was questioning whether foot numbness was worsening.

The log shows a point three months ago when I was taking 5 mg of Kirkland MB-12. At that time, I was one week off of the second trial (which lasted two weeks) of 3mg of AB-12. I was also one week into a 99mg dose of potassium, the first potassium I had taken. (I routinely eat two bananas each day, all totaling about 1,000 mg of K at that time.)

I’m hopeful that my system will respond as it did then, although my chemistry is clearly not what it was at that time. I intend to stick to this (earlier) regimen plus 400 mg of methylfolate and a complex multivitamin for perhaps up to a month, depending upon how quickly my feet and legs continue to worsen in numbness. However, if this level of methylation doesn’t hold the line on even collateral symptoms, I will step up the MB-12 in concert with corresponding amounts of potassium and methylfolate, per recommendations.

I think this is my best play. I am interested in hearing opinions on this plan, contrary or not.

Meanwhile, the Lyme/co-infection tests are a good idea.

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I have lyme and co infections, my issues are pretty severe because of it too. I would look into that for your daughter on top of yourself, eight years is a LONG time to be bedridden after all. A lot of what you described could just be low potassium though. Because you mentioned your feet being the most effected especially. Low Potassium can cause numbness and tingling but another thing you mentioned is the feeling of being in a glove or sock.. Well tight muscles and cramps can kind of trigger this too without any actual nerve damage itself, of course issues with nerves can too. I just had personal experiences with that exact feeling from actually having pretty low potassium thus tight constricted muscles, also your nerves won't fire and communicate as well. The RDV is 4000mg so try and bump it up to actually get yourself covered from low level symptoms. Also be sure to raise your magnesium levels as this goes hand in hand with low potassium, not as oftenly discussed here for some reason. Just something to look into.

I have had over the past months, as I began titrating up MB-12, muscle aches which subsided within hours of taking a 99mg tablet of potassium. Notwithstanding what I blogged yesterday, this AM I took 495 mg of potassium and 1,600 mcg of methylfolate. I also reduced the MB-12 to 10,000 mcg, to keep the ratios more in line.

I do see that the RDA for potassium is over 4,000 mg, so, as you rightly point out, I may still be on the low side assuming an unsupplemented intake somewhere below the amount consumed in a typical diet.

By this morning the numbness had again increased noticeably in my legs. But interestingly, the renewed deficits (of the past month) are largely sensory and not motor, new for me for this syndrome. Perhaps this does suggest a realignment between MB-12, methylfolate, and potassium is appropriate and might be restorative.

[edited] I found the NSCG to Freddds Protocol (thanks). I believe it is time for me to get onboard. I'll provide updates.

I have had over the past months, as I began titrating up MB-12, muscle aches which subsided within hours of taking a 99mg tablet of potassium. Notwithstanding what I blogged yesterday, this AM I took 495 mg of potassium and 1,600 mcg of methylfolate. I also reduced the MB-12 to 10,000 mcg, to keep the ratios more in line.

I do see that the RDA for potassium is over 4,000 mg, so, as you rightly point out, I may still be on the low side assuming an unsupplemented intake somewhere below the amount consumed in a typical diet.

By this morning the numbness had again increased noticeably in my legs. But interestingly, the renewed deficits (of the past month) are largely sensory and not motor, new for me for this syndrome. Perhaps this does suggest a realignment between MB-12, methylfolate, and potassium is appropriate and might be restorative.

[edited] I found the NSCG to Freddds Protocol (thanks). I believe it is time for me to get onboard. I'll provide updates.

Yes it may well be some kind of de tox reaction or potassium/magnesium issues. Though your potassium levels are already at a pretty normal and healthy range. It does not fully account the cellular level but shows its not extremely low. However, these recent issues were with higher does in what you are taking and I do not know if that test was taken during that time period or prior. It seems unlikely that your nervous system issues got substantially worse out of nowhere, while still using things to heal it. It is possible to be a healing reaction where a temporary gain in symptoms means repairing in the CNS system. If you had lyme it could be a herx reaction from de tox, or again just simple low potassium.

By the way be careful with B6, even the P5P form, there are studies showing it can cause nerve damage/issues in pretty high doses or from using supplements with it for a very extended period of time. Usually keeping 10mg max a day is not a problem but anything more can lead to potential issues and I would avoid it. This is still being very consservative but its good to be safe, some people are even sensitive and react to the smaller doses. It is because it is not a natural vitamin as in food but created. Even P5P is not the same kind of make up of vitamin b6 you would find in say pistachios, bananas, eggs, sunflower seeds, etc.. Other then that it seems you are in a very good place and I wish you the very best on you're healing journey.

I have had over the past months, as I began titrating up MB-12, muscle aches which subsided within hours of taking a 99mg tablet of potassium. Notwithstanding what I blogged yesterday, this AM I took 495 mg of potassium and 1,600 mcg of methylfolate. I also reduced the MB-12 to 10,000 mcg, to keep the ratios more in line.

I do see that the RDA for potassium is over 4,000 mg, so, as you rightly point out, I may still be on the low side assuming an unsupplemented intake somewhere below the amount consumed in a typical diet.

By this morning the numbness had again increased noticeably in my legs. But interestingly, the renewed deficits (of the past month) are largely sensory and not motor, new for me for this syndrome. Perhaps this does suggest a realignment between MB-12, methylfolate, and potassium is appropriate and might be restorative.

[edited] I found the NSCG to Freddds Protocol (thanks). I believe it is time for me to get onboard. I'll provide updates.

Potassium was one of those surprises that came along the way in debugging nutrition. Potassium is "supposed" to work as a fast buffer (serum) and a slow buffer (tissues). As current needs are filled from serum more is supposed to replace it from the tissues. Have talked and observed thousands of people with FMS/CFS/ME during the past 11 years, there are several items that stick out like a sore thumb. This potassium issue is one of them. It appears that it could be a defining feature. For some reason a lot of people with FMS/CFS/ME have slower than usual replenishment of serum potassium from tissue potassium. I know people who had all these symptoms because of lack of absorption or lack of existence in diet of the b12s. They usually did not have these same potassium problems, as long as they got enough potassium at any time in their diet and it was available in their tissues. Where those of us with FMS/CFS/ME characteristics often have to take 3-5 doses a day to balance out our own serum potassium because the body isn't doing it well. This appears to be a distinguishing feature, pragmatically determined. It turned out to be a major set of symptoms that people not familiar with this idea called "detox". It appears that better than 90% of what people call "detox" when starting b12 and folates, in many variations for various reasons, is either low folate or low serum potassium or both.

Having sensory changes in all this is usually indicative that the MeCbl is doing its work on the nerves.

"
Based on this paradigm, we propose that the high serum MMA associated with the combination of low B12 status and high plasma folate status stems from the disruption of B12 hemostasis in the mitochondria, analogous to the effect of nitric oxide.
"

I would suggest that you may find Carmen Wheatley's THE GIANT GORILLA IN THE ROOM, ADENOSYLCOBALAMIN very interesting. It is about AdoCbl being the complete inflammation resolution and NO control unlike the starvation work around of HyCbl that is only a partial solution. In practice most people have restoration of mitochondrial function and proliferation required for muscle growth and healing with the Deadlock Quartet and other cofactors. Serum folate accumulates with lack of MeCbl or because it isn't l-methylfolate but rather unconverted folic acid, folinic acid or plant folates which actually block methylfolate. High serum MMA (and in some diseases CSF MMA elevation and homocysteine elevation) are all connected to ME, FMS, CFS, Parkinson's, MS, ALS, (Progressive) Supra Nuclear Palsy, autism and Alzheimer's.

When distributed by diffusion with direct injections or sublingual absorption of the active b12s, much of the biochemistry they speak in that paper of transporting cobalamin via HTC II and converting this or that to the form needed which many people do not do well, simply disappears as a consideration. HTC II can't supply enough MeCbl or AdoCbl to provide rapid and maybe complete healing. This approach is because of the misidentification of B12 as Cyanocobalamin back in 1947-48 due to a lab mistake and not ever corrected despite knowing what the real b12s were as of 1959.

I've been searching for the solutions to these problems since 1979 and confirmed my hypothesis with desiccated liver back then. The active b12s and mfolate were not available until the past 15 years or so.